Minimizing Variability of Cascade Impaction Measurements in Inhalers and Nebulizers

The purpose of this article is to catalogue in a systematic way the available information about factors that may influence the outcome and variability of cascade impactor (CI) measurements of pharmaceutical aerosols for inhalation, such as those obtained from metered dose inhalers (MDIs), dry powder inhalers (DPIs) or products for nebulization; and to suggest ways to minimize the influence of such factors. To accomplish this task, the authors constructed a cause-and-effect Ishikawa diagram for a CI measurement and considered the influence of each root cause based on industry experience and thorough literature review. The results illustrate the intricate network of underlying causes of CI variability, with the potential for several multi-way statistical interactions. It was also found that significantly more quantitative information exists about impactor-related causes than about operator-derived influences, the contribution of drug assay methodology and product-related causes, suggesting a need for further research in those areas. The understanding and awareness of all these factors should aid in the development of optimized CI methods and appropriate quality control measures for aerodynamic particle size distribution (APSD) of pharmaceutical aerosols, in line with the current regulatory initiatives involving quality-by-design (QbD)

17-OHPC to Prevent Recurrent Preterm Birth in Singleton Gestations (PROLONG Study): A Multicenter, International, Randomized Double-Blind Trial

Background âwomen with a history of spontaneous preterm birth (SPTB) are at a significantly increased risk for recurrent preterm birth (PTB). To date, only one large U.S. clinical trial comparing 17-OHPC (17-α-hydroxyprogesterone caproate or 17P) to placebo has been published, and this trial was stopped early due to a large treatment benefit. Objective âThis study aimed to assess whether 17-OHPC decreases recurrent PTB and neonatal morbidity in women with a prior SPTB in a singleton gestation. Study Design âThis was a double-blind, placebo-controlled international trial involving women with a previous singleton SPTB (clinicaltrials.gov: NCT 01004029). Women were enrolled at 93 clinical centers (41 in the United States and 52 outside the United States) between 16 0/7 to 20 6/7 weeks in a 2:1 ratio, to receive either weekly intramuscular (IM) injections of 250 mg of 17-OHPC or an inert oil placebo; treatment was continued until delivery or 36 weeks. Co-primary outcomes were PTB < 35 weeks and a neonatal morbidity composite index. The composite included any of the following: Neonatal death, grade 3 or 4 intraventricular hemorrhage, respiratory distress syndrome, bronchopulmonary dysplasia, necrotizing enterocolitis, or proven sepsis. A planned sample size of 1,707 patients was estimated to provide 98% power to detect a 30% reduction in PTB < 35 weeks (30% to 21%) and 90% power to detect a 35% reduction in neonatal composite index (17%-11%) using a two-sided type-I error of 5%. Finally, this sample size would also provide 82.8% power to rule out a doubling in the risk of fetal/early infant death assuming a 4% fetal/early infant death rate. Analysis was performed according to the intention-to-treat principle. Results âaseline characteristics between the 1,130 women who received 17-OHPC and 578 women who received placebo were similar. Overall, 87% of enrolled women were Caucasian, 12% had >1 prior SPTB, 7% smoked cigarettes, and 89% were married/lived with partner. Prior to receiving study drug, 73% women had a transvaginal cervical length measurement performed and <2% had cervical shortening <25 mm. There were no significant differences in the frequency of PTB < 35 weeks (17-OHPC 11.0% vs. placebo 11.5%; relative risk = 0.95 [95% confidence interval (CI): 0.71-1.26]) or neonatal morbidity index (17-OHPC 5.6% vs. placebo 5.0%; relative risk = 1.12 [95% CI: 0.68-1.61]). There were also no differences in frequency of fetal/early infant death (17-OHPC 1.7% vs. placebo 1.9%; relative risk = 0.87 [95% CI: 0.4-1.81]. Maternal outcomes were also similar. In the subgroup of women enrolled in the United States (n = 391; 23% of all patients), although the rate of PTB < 35 weeks was higher than the overall study population, there were no statistically significant differences between groups (15.6% vs. 17.6%; relative risk = 0.88 [95% CI: 0.55, 1.40]. Conclusion âin this study population, 17-OHPC did not decrease recurrent PTB and was not associated with increased fetal/early infant death

Development of water and wastewater infrastructure in Lublin province in 2000-2011

W pracy przeprowadzono analizę rozwoju infrastruktury wodno-ściekowej w woj. lubelskim w latach 2000-2010. Ponadto na podstawie wyników badań ankietowych, wykonanych w 70 wybranych gminach województwa, przedstawiono stan podstawowych elementów infrastruktury wodno-ściekowej w 2011 r. Stwierdzono dużą dysproporcję pomiędzy rozwojem sieci wodociągowej i kanalizacyjnej na terenach wiejskich woj. lubelskiego w pierwszej dekadzie XXI wieku. Odnotowano, że w 2011 r. w wybranych gminach województwa (głównie wiejskich) z sieci wodociągowej korzystało 84,8% ludności, a z sieci kanalizacyjnej tylko 18,6%. W latach 2000-2010 w woj. lubelskim odnotowano stopniowy postęp w zakresie budowy sieci kanalizacyjnych, a szczególnie w przypadku zbiorowych i przydomowych oczyszczalni ścieków, który był możliwy głównie dzięki funduszom unijnym pozyskanym przez jednostki samorządowe. W analizowanym okresie wśród zbiorowych oczyszczalni ścieków najczęściej stosowano oczyszczalnie biologiczne, a w przypadku obiektów przydomowych - systemy z drenażem rozsączającym.The paper presents analyzes the development of water and sewage infrastructure in the Lublin province in 2000-2010. In addition, based on the results of surveys carried out in 70 selected municipalities province, presents the state of the basic elements of water and sewage infrastructure in 2011. Found a large disparity between the development of water supply and sanitation in rural of Lublin province in the first decade of the twenty-first century. It was noted that in 2011 in selected municipalities of the region (mainly rural) water supply system has benefited 84.8% of the population, and the sewerage system only 18.6%. In the years 2000-2010 in the Lublin province has been gradual progress the construction of sewerage systems, and particularly in the case of collective and sewage treatment plants, which was possible mainly thanks to EU funds acquired by local governments. In the analyzed period, the collective biological waste water treatment plants were the most commonly used, in the case of household objects - infiltration drainage systems

Native and Methylated Cyclodextrins with Positive and Negative Solubility Coefficients in Water Studied by SAXS and SANS

While the solubility of native alpha-, beta-, gamma-cyclodextrins (CDs) in water rises with temperature, the opposite is true for their methylated derivatives (mCDs; per-dimethylated beta-CD and per-trimethylated gamma-CD). The mCDs are well-soluble in cold water and crystallize upon heating, which we associate with the hydrophobic effect. To study the hydrophobic effect and hydration of CDs and mCDs dissolved in water (D 2O), we performed small-angle X-ray and neutron scattering (SAXS and SANS) measurements. The experimental scattering curves were put on absolute scale and compared to scattering curves calculated from crystal structures using the cube method. The results of the comparison indicate that (i) in solution, CDs and mCDs are in monomeric form, (ii) van der Waals and solute excluded volumes can be related by introducing a shell of a thickness that correlates with the solute's structure and solute-water interactions, and (iii) the SAXS curves calculated under the assumption of a uniform distribution of electron density in the solute molecules agree with experimental ones for CDs, but not for mCDs. The temperature and concentration dependence of SAXS curves is significant for mCDs and weak for CDs and is discussed in terms of solute-solute interactions. Specifically, these interactions become more attractive in solutions of mCDs with increasing temperature, concentration, or both, in accord with mCDs' negative temperature coefficient of solubility in water